This UCLA Symposium entitled "Manipulating the Mammalian Genome" will address the major advances seen in the past several years in our ability to analyze the structure of large and complex mammalian genomes and to identif and characterize the genes that underlie various human diseases. Paralleling these advances in the analysis of genome structure have been major advances in techniques for cultivating and manipulating mouse germ line cells, and for making specific mutations in cultured mammalian cells. This technology will allow rapid progress in mammalian developmental genetics and in our functional understanding of the mammalian genome. Any gene of known sequence can potentially be altered by homologous recombination. Application of these techniques to mouse embryonic stem (ES cells followed by generation of mice from the altered cells allows determination of the effects of any mutation in mice. The role of specific genes in development can be examined, and alteration of mouse genes homologous to those involved in human disease will allow rapid development of animal models for human disease. This meeting will explore advances in these structural and functional technologies, their application to developmental questions, advances in human genome mapping and biology, and attempts to correct human disease by genetic alteration of somatic cells. The meeting will facilitate communication in the rapidly progressing fields of muse genetics and human biology and disease.